Organ Tx

Tianjin Medical University General
器官移植
Organ Transplantation
Introduction of Organ Tx
Brief of Various Organ Txs

Pittsburgh, PE

UP
chimerism

Study in UPMC

Organ Tx —— A Kind of Myth
1515 世纪意大利诗人世纪意大利诗人 CalenzioCalenzio 描述描述
奴隶为主人献出自己的鼻子奴隶为主人献出自己的鼻子
传说传说 300 B.C.300 B.C. 扁鹊为鲁国的公扈、扁鹊为鲁国的公扈、
赵国的齐婴换心赵国的齐婴换心

Organ Tx —— A Kind of Myth
A Chinese document written in approximately 300 B.C.
contains this legendary of transplantation: “One day two
men, Lu and Chao, called on the surgeon Pien Ch’iao.
He gave them toxic drinks and they were unconscious for
three days. Pien Ch’iao operated and opened their
stomachs and explored the heart; after removing and
interchanging their organs he gave a wonderful drug and
the two men went home recovered.”
R. Randal Bollinger, et al. Chapter 20 “Transplantation”
Textbook of Surgery, 2003

History
• Alexis Carrel (1873~1944) is known as
the founding father of experimental
organ transplantation because of his
pioneering work with vascular
techniques.
 1902 Carrel & Guthrie 首次用血管缝合法行多个脏器移植的动物实验
 1912 Carrel 因血管吻合、输血和器官移植获 Nobel 生理学和医学奖
• Frank Mann (1887–1962) studied renal and heart
transplantation at the Mayo Clinic in the 1930s. Early
transplantation attempts in humans, which began with
transplantation of renal allografts in 1936, generally did
not succeed.

Dawn of Clinical Tx
• 1962 Murray Kidney Tx
• 1963 Starzl Liver Tx
• 1963 Hardy Lung Tx
• 1964 Detterling Small Bowel Tx
• 1966 Kelly Pancreas Tx
• 1967 Barnard Heart Tx
• 1968 Cooley Heart/Lungs Tx （ Thorax en bloc ）
• 1989 Starzl Multivisceral Tx （ Abdomen en bloc ）
• 1989 Grant Liver/Small Bowel Tx

Definition
• A procedure in a human or animal in which a body cell,
tissue or organ is transferred from a donor to a
recipient or from one part of the body to another in
order to treat life-threatening illness.
• Graft: active cell, tissue or organ
• Access: surgery / others
• Individual: oneself / other perpson
• Location: anatomic / another
location
• To maintain native function and
viability

Terminology
• Organ Tx
• Graft
• Donor
• Recipient
• Donation
• Implantation
• Replantation
Organ transplantation is the process of removal
and transplantation of viable organs from one
individual to another or him/herself via vessels
anastomosis. In this process, transplanted viscera
must keep viability and function. The individuals of
donating and receiving have to be matched in
transplant antigens in order to reduce the episodes
of rejection in the new organ.

Classification
• Hereditary Deriving
 autotx, the donor and recipient is the same
individual.
 isotx or syngeneic graft, the donor and
recipient are genetically identical (eg, mono-
zygotic twins).
 allotx or homogeneic graft, the donor and
recipient are genetically unrelated but belong
to the same species.
 xenotx or heterogeneic graft, the donor and
recipient belong to different species.

Genetics Background
 Autotx Take
 Isotx Take
 Allotx Reject
 Xenotx Reject

Classification
• Location
 Orthotopic Tx refers to donor organ implanted
in the anatomically correct position in the
recipient.
 Heterotopic Tx refers to the relocation of the
implant in the recipient at a site different from
the normal anatomy.
 Paratopic Tx refers to graft implanted in close
location to organ which will be replaced, and
recipient’s organ is not removed.

Classification
• Types of Graft
 Cell
 Tissue
 Organ
• Approach of Tx
 Blood Vessel
Reconstruction
 Implanting
 Transfusion

Transplant Immunology
• Transplant Antigen
 ABO blood group antigen
 Major histocompatibility antigen
(human leukocyte antigen)
 Minor histocompatibility antigen
 Tissue different antigen

Major Histocompatibility Complex

Presentation & Recognition
• CD4+ T cells
associating with
different deriving
antigen presentation
cells (macrophage and
dentritic cell) recognize
alloantigens in intact or
processed forms.

Activation & Effect
• CD4+ T cells
recognizing
alloantigens
contribute to the
rejection process
by providing help
to CD8+ cytotoxic
T cells and
alloantibody-
producing B cells.

Immune Response

Immune Reaction
Direction
Graft against Host
Direction
Host against Graft

Various Immune Respond
• Rejection
 Hyperacute rejection
 Accelerative rejection
 Acute rejection
 Chronic rejection
• GVHD
 Acute GVHD
 Chronic GVHD

Common Aspects
• Acute rejection usually occurs days to weeks
after transplantation. It is initiated by T-cell-
dependent immunity and is characterized
microscopically by a lymphocytic infiltrate
accompanied by plasma cells, eosinophils, and
a few mast cells or neutrophils.
• Chronic rejection usually occurs months to
years after transplantation. It is characterized
by loss of normal histologic structure, fibrosis,
and atherosclerosis.

Diagnosis
1. Fever, fatigue, anorexia, as well as swollen and
painful area of graft location.
2. Aberrant graft function and drainage.
3. Fine needle aspiration (FNA) or endoscopy
biopsy demonstrating amount of lymphocytes
infiltrating graft.
4. Abnormal radiologic study.
5. Alteration of the ratio of CD4:CD8 in
recipients’ peripheral blood T cell and high
expression of various antibodies and
cytokines.
6. Decreasing blood concentration of immuno-
suppressant.

Diagnosis

Golden Standard of Rejection
• Tissue samples are typically obtained by needle
aspiration guided with image and endoscopy
via the way of surgically placed stoma.
• Many transplant protocols require tissue
biopsies to be performed on the transplanted
organ.
• Rejection can be patchy, which mandates that
tissue biopsies were taken from several sites.

Immunosuppression
• The major objective of immunosuppressive therapy is
thus to prevent acute allograft rejection.
• This goal must be balanced by the risks of
immunosuppression, especially opportunistic infection
and neoplasia.
• Both of these are considered in more depth later.
• Because the immune system recognizes foreign
alloantigen so quickly, clinical immunosuppression is
started before surgery.
• Large doses of corticosteroids are usually given at this
stage.
• The use of induction therapy with polyclonal or mono-
clonal antibody preparations is still debated, but
appears to have advantages.

Chemical Agents
• Corticosteroids
• Proliferation Inhibitor
 Azathioprine, AZA
 Cyclophosphamide ， Cys
 Mycophenolate mofetil, MMF
• Calcineurin Inhibitor
 Cyclosporine, CsA (one of millstone of organ Tx)
 Tacrolimus, Prograf/Fk 506
• Target of Rapamycin Inhibitor
 Sirolimus
 Everolimus

Mechanism of CNI & TORI
CNI: Calcineurin Inhibitor
TORi: Target of Rapamycin Inhibitor

Biologic Agents
• Muromonab (OKT3)
• Daclizumab (Zenapax)
• Basiliximab (Simulect)
• Alemtuzumab (Campath-1H)
• Thymoglobulin (antithymocyte globulin)
• Lymphoglobulin (antilymphocyte globulin)
• Preclinical drug ： FTY-720

Protocols of Prophylaxis
• Cyclosporine-based immunosuppression
• Tacrolimus-based immunosuppression
• Rapamycin-based immunosuppression
 Steroids
 Mycophenolate mofetil
 Prostaglandin E1

Approach of Retrieval Treatment
• Administrating large dose
corticosteroids in bolus.
• Replacing CsA with FK-506 or RAPA.
• Adding RAPA.
• Using muromonab (OKT3), as well as
other antibody, such as ALG or ATG.

Immune Tolerance
• Successful Tolerance Criteria
 No immunosuppression administration
 No rejection episodes
 No infection occurrences
• Almost Tolerance
 Liver transplantation (chimerism
between graft and recipient)

Surgical Aspect
• Donor Selection
 Physiologic & social conditions
 Tissue match
• Graft Procurement
• Perfusion
• Preservation
• Bench Work (Back Table)
• Recipient Operation

Donor
• Donor Age
 Fetus
 Newborn
 Adult
• Donor Viability
 Cadaveric
 Non-heart-beating
 Brain Death
 Living
 Related
 Spouse
 Non-related

Tissue Match
• Blood Group Antigen (ABO)
• Lymphocytotoxicity Test (death cells<10%)
• Mix Lymphocyte Culture (transfer rate<30%)
• Panel Reactive Antibody
• Human Leukocyte Antigen (HLA)
• Endothelial Antigen

Removal

Perfusion
• Purposes
 Speedy Hypothermia
 Flushing out Residual Donor Blood
• Approaches
 In vivo perfusion
 In vitro perfusion
• Solution
 0 ～ 4 (ice℃ scraps)
 Heparinized

Preservation
• Principles
 Hypothermia
 Maintain Moderate Osmotic Pressure
 Reducing Reperfusive Injure
• Solutions
 Intracellular: Euro-Collins, UW Solution
 Extracellular: Hartmann, Celsior
 Others: HTK (histidinetryptophan ketoglutarate)
• Approaches
 Simple hypothermia
 Continuous mechanical perfusion
 Freezing hypothermia

Preservation
• Belger (1987)
UW (University of Wisconsin) solution can
preserve kidney, pancreas 72 hrs and store
liver 20-24 hrs, intestine 18 hrs.
• Providing time possibility of
grafts intercontinental transffer
• Another mailstone of organ
transplantation

HTK vs UW
• HTK delivery in normal temperature
• Storage at 0-4℃
• Flush volume is 6-8L and short warm
ischemic time
• Flushing vascular plexus more effectively
• Graft cold preserving time up to 18 hrs
safely (LIVER)
• Normal K+ concentration, not need flush
with Ringer’s Sol before reperfusion
• Cost 40-50% less than UW

-
-
60
-
30
20
-
3
-
-
-
80
-
0.25
13
15
100
Celsior
310320355Osmolalrity (mOsm/L)
2--Tryptophan (mmol/L)
--194Glucose (mmol/L)
30--Mannitol (mmol/L)
-50-Starch (gm/L)
198--Histidine (mmol/L)
1--Ketoglutarate/Glutamic Acid (mmol/L)
-1-Allopurinol (mmol/L)
-3-Glutathione (mmol/L)
-5-Adenosine (mmol/L)
-30-Raffinose (mmol/L)
-2557Phosphate (mmol/L)
-100-Lactobionate (mmol/L)
-5-Sulfate (mmol/L)
0.015--Calcium (mmol/L)
45-Magnesium( mmol/L)
10120107Potassium (mmol/L)
154010Sodium (mmol/L)
HTKUWEurocollinsComponent
Comparison of various solutions for organ preservation

Back Table Operation
conduit

Recipient Operation

Kidney Transplantation

Liver Transplantation
Liver Cirrhosis
Transplanted Liver

Piggy Back Liver Tx

Cavaplastic Liver Tx

Small Bowel Tx
Portal Vein Outflow Systemic Outflow

Pancreas Tx
Back-table Prepare
Blood Vessels
Anastomosis
Bladder Drainage Gut Drainage

Heart Transplantation
Orthotopic Transplantation Paratopic Transplantation

Lung Transplantation

Semina of Successful Tx
• 移植免疫理论的建立
Establishing of transplant immunology
• 免疫抑制药物的发现
Discovery of immunosuppressive drugs
• 外科手术技术的提高
Improving of surgical skill
• 器官保存溶液的诞生
Emerging of organ perfusion solution
• 临床相关学科的进步
Progressing of relative clinic sciences

Continued Increasing Number of
Organ Transplantation
’97 ’99 ’00 ’03 ’06
Kidney 415,854 473,597 500,545 >100×104
KP 7,559 10,145 11,541 13,917
Pancraes 2,260 3,070 >20,000
Liver 62,502 80,221 89,178
Heart 46,227 55,359 57,043 66,353
Lung 7,689 11,148 12,076 17,128
HL 2,698 3,049
Bowel/LB/MV 273 474 654 1,125 >1,200
Bone Marrow 75,212 88,909
Total 617,626 725,621
(Worldwide Transplant Center Directory ,WTCD 全球移植中心名录 )

Barrier of Organ transplantation
• Donor Shortage
www.CartoonStock.com

Living Donor
• advantages
 performing when the
recipient is in the best
condition
 minimizing ischemia times
 In genetic relation, reducing
the degree of genetic
incompatibility
• disadvantages
 Insufficient size transplanting
 residual organ in the donor be
not adequate to ensure
satisfactory function
 putting the donor at risk of
morbidity

Grafts Sharing

Xenograft

Legislation of Brain Death

• Chronic Rejection

• Xenorejection

How to be a Transplant Surgeon
• 仁慈博爱
• 端极负责
• 勤耐奋劳
• 广博知识
• 信念坚实
• 良好心理
• 精神团队
• 熟技巧娴

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Organ Tx

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